The fire was reported just after 5:30 p.m. in the 1000 block of Hildebidle Drive in Collegeville.
Flames were shooting through the roof of the house
Firefighters used ladder trucks and torrents of water to douse the blaze which was under control by 6:30 p.m.
A 12-year-old girl and 46-year-old man were taken to Albert Einstein Medical Center Montgomery for treatment.
A 13-year-old girl was treated at the scene for smoke inhalation.
The Red Cross is assisting the family of four displaced by the fire.